With the exception of transferrin, desialylated serum glycoproteins are promptly removed from the circulation by the parenchymal cells of the liver. The primary binding site for the asialoproteins has been identified as the liver plasma membrane and the parameters of glycoprotein binding in vitro closely parallel those required for clearance in vivo. An in vitro assay system has been developed which is capable of providing a quantitative measure of binding and which provides an experimental model for a detailed examination of the structural determinants of glycoprotein binding as well as the binding phenomenon itself. Although termination of the carbohydrate chains by intact, nonreducing galactose is a major determinant of binding and clearance, it is neither unique nor sufficient to explain the broad spectrum of glycoprotein binding behavior observed. The role of the protein backbone, the participation of critical amino acids present in oligosaccharide chains, all require quantitative evaluation. The proposed investigation will provide such information on the additional structural determinants of binding.